Flagellar rotation is one of the major mechanisms for bacterial mobility, and is essential for biofilm formation. Many bacteria use the transmembrane electrochemical gradient (H+ or Na+) to power rotation of the transmembrane flagellar motor. There are extensive but separate experimental and modeling efforts on BFM torque generation and CW-CCW switching. However, recently the Berg lab observed that the motor switch dynamics is affected by the load as well as chemotactic signals. A motor switching frequency increases first but then decreases upon increasing the external load. This phenomenon is suggested to have functional roles. Understanding these results requires a unified treatment of torque generation and switching. In this proposed research, we aim at constructing an integrated model describing flagellar motor switching and torque generation based on available experimental data, with the following three specific aims: 1) Construct a mathematical model and examine mechanism for the load-dependent switching dynamics. We will generalize the conformational spread model by including the dependence of switching rates on motor torque, which is obtained directly from the measured torque-speed relations, and evaluate various mechanisms. Preliminary studies have confirmed validity of the procedure. 2) Examine possible functional roles of load-dependent switching dynamics. We will use the models developed in Aim 1 and 2 to examine multi-motor dynamics under fluctuating CheY-P concentrations. The proposed research will be performed through collaborating with the labs of Howard Berg (Harvard University), Keiichi Namba (Osaka University), Richard Berry (Oxford University), and David Blair (University of Utah). Corresponding experiments will be performed in these labs. We will systematically examine the existing experimental results, bridge and integrate static structural information and dynamic data, and make testable predictions parallel to the experimental studies in several other labs. It will place studies of BFM functions in the broader context of cell physiology regulations. PUBLIC HEALTH RELEVANCE: Bacteria infection is a global health problem. Understanding the regulation mechanism of flagellar motor based cell motility is important for bacterial pathology. It also provides guidance on researches aimed at modifying the flagellar motor as nanomachines for biomedical functions.